• Title/Summary/Keyword: Motor neurons

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Noradrenergic axons hitch hiking along the human abducens nerve

  • Yusra Mansour;Randy Kulesza
    • Anatomy and Cell Biology
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    • v.56 no.2
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    • pp.271-275
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    • 2023
  • The abducens nerve (AN; cranial nerve VI) exits the brainstem at the inferior pontine sulcus, pierces the dura of the posterior cranial fossa, passes through the cavernous sinus in close contact to the internal carotid artery (ICA) and traverses the superior orbital fissure to reach the orbit to innervate the lateral rectus muscle. At its exit from the brainstem, the AN includes only axons from lower motor neurons in the abducens nucleus. However, as the AN crosses the ICA it receives a number of branches from the internal carotid sympathetic plexus. The arrangement, neurochemical profile and function of these sympathetic axons running along the AN remain unresolved. Herein, we use gross dissection and microscopic study of hematoxylin and eosin-stained sections and sections with tyrosine hydroxylase immunolabeling. Our results suggest the AN receives multiple bundles of unmyelinated axons that use norepinephrine as a neurotransmitter consistent with postganglionic sympathetic axons.

Effect of Parthenogenetic Mouse Embryonic Stem Cell (PmES) in the Mouse Model of Huntington′s Disease

  • 이창현;김용식;이영재;김은영;길광수;정길생;박세필;임진호
    • Proceedings of the KSAR Conference
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    • 2003.06a
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    • pp.80-80
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    • 2003
  • Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by marked cell death in the striatum and cortex. Stereotaxic injection of quinolinic acid (QA) into striatum results in a degeneration of GABAergic neurons and exhibits abnormal motor behaviors typical of the illness. The objective of this study was carried out to obtain basic information about whether parthenogenetic mouse embryonic stem (PmES) cells are suitable for cell replacement therapy of HD. To establish PmES cell lines, hybrid F1 (C57BL/6xCBA/N) mouse oocytes were treated with 7% ethanol for 5 min and cytochalasin-B for 4 hr to initiate spontaneous cleavage. Thus established PmES cells were induced to differentiate using bFGF (20ng/ml) followed by selection of neuronal precursor cells for 8 days in N2 medium. After selection, cells were expanded at the presence of bFGF (20 ng/ml) for another 6 days, then a final differentiation step in N2 medium for 7 days. To establish recipient animal models of HD, young adult mice (7 weeks age ICR mice) were lesioned unilaterally with a stereotaxic injection of QA (60 nM) into the striatum and the rotational behavior of the animals was tested using apomorphine (0.1mg/kg, IP) 7 days after the induction of lesion. Animals rotating more than 120 turns per hour were selected and the differentiated PmES cells (1$\times$10$^4$cells/ul) were implanted into striatum. Four weeks after the graft, immunohistochemical studies revealed the presence of cells reactive to anti-NeuN antibody. However, only a slight improvement of motor behavior was observed. By Nissl staining, cell mass resembling tumor was found at the graft site and near cortex which may explain the slight behavioral improvement. Detailed experiment on cell viability, differentiation and migration explanted in vivo is currently being studied.

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A Case Report of a Patient with Parkinson's Disease Treated with Acupuncture and Exercise Therapy (침 및 운동 치료로 호전된 파킨슨병 환자 1례에 대한 증례보고)

  • Park, Miso;Park, SangSoo;Lee, Seung Hyun;Hur, WangJung;Yoo, Horyong
    • The Journal of Internal Korean Medicine
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    • v.43 no.5
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    • pp.1018-1028
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    • 2022
  • Objectives: Parkinson's disease is characterized by progressive, irreversible damage to dopamine neurons in the substantia nigra pars compacta, as well as motor and non-motor symptoms. This disease currently has no dependable disease-modifying treatment. In this paper, we describe the treatment of a 67-year-old female with Parkinson's disease using acupuncture and exercise therapy. Case Presentation: Clinical symptoms and the United Kingdom Parkinson's Disease Society Brain Bank Diagnostic Criteria were used to diagnose the patient with Parkinson's disease. Over a 12-week period, the patient visited a Korean medicine hospital 18 times and was treated with acupuncture and exercise therapy in addition to anti-Parkinson's drugs. Before and after treatment, clinical examinations were performed using tools such as the Unified Parkinson's Disease Rating Scale, Fall Efficacy Scale, Parkinson's Disease Questionnaire, Berg Balance Scale, and Non-Motor Symptoms Scale. Furthermore, functional near-infrared spectroscopy was used to assess cortical hemodynamics. All clinical examination results improved after 12 weeks of intervention. In particular, improvements on the Total Unified Parkinson's Disease Rating Scale and Part III of this scale demonstrated large, clinically important differences. Conclusion: This case suggests that combining acupuncture and exercise therapy could produce an effective treatment for Parkinson's disease patients.

Facilitated Axonal Regeneration of Injured Sciatic Nerves by Yukmijihwang-tang Treatment

  • Kim, Jung-Hyun;Seol, In-Chan;Ryu, Ho-Ryong;Jo, Hyun-Kyung;An, Joung-Jo;Namgung, Uk;Kim, Yoon-Sik
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.4
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    • pp.896-902
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    • 2008
  • Yukmijihwang-tang(YM) is used in Oriental medicine for treatments of diverse systemic symptoms including neurological dosorders. The present study was performed to examine potential effects of YM on growth-promoting activity of injured sciatic nerve axons. YM treatment in the injured sciatic nerve induced enhanced distal elongation of injured axons when measured 3 and 7 days after injury. Retrograde tracing of sciatic nerve axons showed YM-mediated increases in the number of DiI-labeled dorsal root ganglion (DRG) sensory neurons and spinal cord motor neurons at 3 days after injury. Hoechst nuclear staining showed that non-neuronal cell population was largely elevated by YM treatment in distal nerve area undergoing axonal regeneration. Furthermore, phospho-Erk1/2 protein levels were upregulated by YM treatment in the injured nerve area. These data suggest that YM may play a role in facilitated axonal regeneration in injured peripheral nerves. Further investigations of individual herbal components would be useful to explore effective molecular components and develop therapeutic strategies.

Neuroprotective Effect of β-Lapachone in MPTP-Induced Parkinson's Disease Mouse Model: Involvement of Astroglial p-AMPK/Nrf2/HO-1 Signaling Pathways

  • Park, Jin-Sun;Leem, Yea-Hyun;Park, Jung-Eun;Kim, Do-Yeon;Kim, Hee-Sun
    • Biomolecules & Therapeutics
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    • v.27 no.2
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    • pp.178-184
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    • 2019
  • Parkinson's disease is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons within the substantia nigra pars compacta. In the present study, we investigated whether ${\beta}-Lapachone$ (${\beta}-LAP$), a natural naphthoquinone compound isolated from the lapacho tree (Tabebuia avellanedae), elicits neuroprotective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. ${\beta}-LAP$ reduced the tyrosine hydroxylase (TH)-immunoreactive fiber loss induced by MPTP in the dorsolateral striatum, and alleviated motor dysfunction as determined by the rotarod test. In addition, ${\beta}-LAP$ protected against MPTP-induced loss of TH positive neurons, and upregulated B-cell lymphoma 2 protein (Bcl-2) expression in the substantia nigra. Based on previous reports on the neuroprotective role of nuclear factor-E2-related factor-2 (Nrf2) in neurodegenerative diseases, we investigated whether ${\beta}-LAP$ induces upregulation of the Nrf2-hemeoxygenae-1 (HO-1) signaling pathway molecules in MPTP-injected mouse brains. Western blot and immunohistochemical analyses indicated that ${\beta}-LAP$ increased HO-1 expression in glial fibrillary acidic protein-positive astrocytes. Moreover, ${\beta}-LAP$ increased the nuclear translocation and DNA binding activity of Nrf2, and the phosphorylation of upstream adenosine monophosphate-activated protein kinase (AMPK). ${\beta}-LAP$ also increased the localization of p-AMPK and Nrf2 in astrocytes. Collectively, our data suggest that ${\beta}-LAP$ exerts neuroprotective effect in MPTP-injected mice by upregulating the p-AMPK/Nrf2/HO-1 signaling pathways in astrocytes.

Matrix Metalloproteinase-8 Inhibitor Ameliorates Inflammatory Responses and Behavioral Deficits in LRRK2 G2019S Parkinson's Disease Model Mice

  • Kim, Taewoo;Jeon, Jeha;Park, Jin-Sun;Park, Yeongwon;Kim, Jooeui;Noh, Haneul;Kim, Hee-Sun;Seo, Hyemyung
    • Biomolecules & Therapeutics
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    • v.29 no.5
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    • pp.483-491
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    • 2021
  • Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

Effect for Wellness of Blood Flow Restriction Aerobic Exercise Program - Focusing on Mscle Ativity and Mtor Nurons - (혈류제한 유산소운동 프로그램의 웰니스를 위한 효과검정 - 근활성도와 운동신경원을 중심으로 -)

  • Jeong, Dae-Keun;Kang, Jeong-Il;Jang, Jun-Min
    • Journal of Korea Entertainment Industry Association
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    • v.15 no.7
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    • pp.225-233
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    • 2021
  • This study quantitatively compares and analyzes lower extremity muscle activity and motor neurons by performing blood flow-restricting aerobic training in the lower extremities, which is closely related to aerobic capacity for health, in normal people, and provides basic data to suggest the effectiveness of an effective blood-restricting exercise program. would like to provide A group of 10 people who applied aerobic exercise on a treadmill by restricting blood flow to 140 mmHg of pressure was set as Experimental Group I. And 11 people who applied only aerobic exercise on a treadmill were randomly assigned as a control group. The intervention program was implemented on a treadmill for 4 weeks, 3 times a week, once a day, for 30 minutes once. In addition, muscle activity and motor neurons were measured and analyzed using surface electromyography before intervention. As a result of the study, the muscle activity of the rectus femoris, biceps femoris, tibialis anterior and gastrocnemius was significantly increased (p<.001) in the pre-and-poster comparison within the group of experimental group I (p<.001). In the pre-and-poster comparison of the control group, the muscle activity of the rectus femoris, biceps femoris, tibialis anterior and gastrocnemius was significantly increased (p<.001). In comparison of changes between groups, there was a significant difference in the activity of the rectus femoris muscle (p<.05). Combining aerobic exercise in parallel with lower extremity blood flow restriction can be developed into an injury prevention exercise program that can restore functional activity in rehabilitation training for elite athletes and elderly people with weak joints. In addition, based on these results in future research, it is considered that it is necessary to expand the scope of non-normal subjects and conduct various studies according to the pressure intensity.

Effects of Root of Cibotii Rhizoma on Neuronal Damage of Spinal Cord Contusion Injury in Rats (구척(狗脊)이 흰쥐의 척수압박에 의한 신경세포 손상에 미치는 영향)

  • Park, Won-Sang;Kim, Eun-Seok;Shin, Jung-Won;Kim, Bum-Hoi;Kim, Seong-Joon;Kang, Hee;Sohn, Nak-Won
    • Journal of Korean Medicine Rehabilitation
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    • v.20 no.2
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    • pp.1-15
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    • 2010
  • Objectives : This study was performed to evaluate the effects of root of Cibotii rhizoma(CR) ethanol extract on the tissue and neuronal damage of the spinal cord injury(SCI). Methods : SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. CR was orally given once a day for 7 days after SCI. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue(LFS) histochemistry. HSP72(as neuronal damage marker), MAP2(as nerve fiber degeneration marker), c-Fos(immediate early gene), and Bax(pro-apoptotic molecule) expressions were examined using immuno-histochemistry. Individual immuno-positive cells expressing HSP72, MAP2, c-Fos and Bax were observed on the damaged level and the upper thoracic and lower lumbar spinal segments. Results : 1. CR reduced degeneration of nerve fibers and motor neuron shrinkage in the ventral horn of the lower lumbar spinal segment, but generally it did not seem to ameliorate the tissue injury following SCI. 2. CR reduced demyelination in the ventral and lateral funiculus of the lower lumbar spinal segment. 3. CR reduced HSP72 expression on the neurons in the peri-central canal gray matter adjacent to the damaged region. 4. CR strengthened MAP2 expression on the motor neurons in the ventral horn and on nerve fibers in the lateral funiculus of the lower lumbar spinal segment. 5. CR reduced c-Fos positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. 6. CR reduced Bax positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. Conclusions : These results suggest that CR plays an inhibitory role against secondary neuronal damage and nerve fiber degeneration. following SCI.

Abrogation of the Circadian Nuclear Receptor REV-ERBα Exacerbates 6-Hydroxydopamine-Induced Dopaminergic Neurodegeneration

  • Kim, Jeongah;Jang, Sangwon;Choi, Mijung;Chung, Sooyoung;Choe, Youngshik;Choe, Han Kyoung;Son, Gi Hoon;Rhee, Kunsoo;Kim, Kyungjin
    • Molecules and Cells
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    • v.41 no.8
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    • pp.742-752
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    • 2018
  • Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive degeneration of dopaminergic (DAergic) neurons, particularly in the substantia nigra (SN). Although circadian dysfunction has been suggested as one of the pathophysiological risk factors for PD, the exact molecular link between the circadian clock and PD remains largely unclear. We have recently demonstrated that $REV-ERB{\alpha}$, a circadian nuclear receptor, serves as a key molecular link between the circadian and DAergic systems. It competitively cooperates with NURR1, another nuclear receptor required for the optimal development and function of DA neurons, to control DAergic gene transcription. Considering our previous findings, we hypothesize that $REV-ERB{\alpha}$ may have a role in the onset and/or progression of PD. In the present study, we therefore aimed to elucidate whether genetic abrogation of $REV-ERB{\alpha}$ affects PD-related phenotypes in a mouse model of PD produced by a unilateral injection of 6-hydroxydopamine (6-OHDA) into the dorsal striatum. $REV-ERB{\alpha}$ deficiency significantly exacerbated 6-OHDA-induced motor deficits as well as DAergic neuronal loss in the vertebral midbrain including the SN and the ventral tegmental area. The exacerbated DAergic degeneration likely involves neuroinflammation-mediated neurotoxicity. The $REV-erb{\alpha}$ knockout mice showed prolonged microglial activation in the SN along with the over-production of interleukin $1{\beta}$, a pro-inflammatory cytokine, in response to 6-OHDA. In conclusion, the present study demonstrates for the first time that genetic abrogation of $REV-ERB{\alpha}$ can increase vulnerability of DAergic neurons to neurotoxic insults, such as 6-OHDA, thereby implying that its normal function may be beneficial for maintaining DAergic neuron populations during PD progression.

The Effects of Difumarate Salt S-15176 after Spinal Cord Injury in Rats

  • Erdogan, Hakan;Tuncdemir, Matem;Kelten, Bilal;Akdemir, Osman;Karaoglan, Alper;Tasdemiroglu, Erol
    • Journal of Korean Neurosurgical Society
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    • v.57 no.6
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    • pp.445-454
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    • 2015
  • Objective : In the present study we analyzed neuroprotective and antiapoptotic effect of the difumarate salt S-15176, as an anti-ischemic, an antioxidant and a stabilizer of mitochondrial membrane in secondary damage following spinal cord injury (SCI) in a rat model. Methods : Three groups were performed with 30 Wistar rats; control (1), trauma (2), and a trauma+S-15176 (10 mg/kg i.p., dimethyl sulfoxide) treatment (3). SCI was performed at the thoracic level using the weight-drop technique. Spinal cord tissues were collected following intracardiac perfusion in 3rd and 7th days of posttrauma. Hematoxylin and eosin staining for histopatology, terminal deoxynucleotidyl transferase dUTP nick end labeling assay for apoptotic cells and immunohistochemistry for proapoptotic cytochrome-c, Bax and caspase 9 were performed to all groups. Functional recovery test were applied to each group in 3rd and 7th days following SCI. Results : In trauma group, edematous regions, diffuse hemorrhage, necrosis, leukocyte infiltration and severe degeneration in motor neurons were observed prominently in gray matter. The number of apoptotic cells was significantly higher (p<0.05) than control group. In the S-15176-treated groups, apoptotic cell number in 3rd and 7th days (p<0.001), also cytochrome-c (p<0.001), Bax (p<0.001) and caspase 9 immunoreactive cells (p<0.001) were significantly decreased in number compared to trauma groups. Hemorrhage and edema in the focal areas were also noticed in gray matter of treatment groups. Results of the locomotor test were significantly increased in treatment group (p<0.05) when compared to trauma groups. Conclusion : We suggest that difumarate salt S-15176 prevents mitochondrial pathways of apoptosis and protects spinal cord from secondary injury and helps to preserve motor function following SCI in rats.